Conditional linearizability criteria for a system of third-order ordinary differential equations

We provide linearizability criteria for a class of systems of third-order ordinary differential equations (ODEs) that is cubically semi-linear in the first derivative, by differentiating a system of second-order quadratically semi-linear ODEs and using the original system to replace the second derivative. The procedure developed splits into two cases, those where the coefficients are constant and those where they are variables. Both cases are discussed and examples given

The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer and affected relatives

The purpose of this study was to determine the prevalence of BRCA1 mutations in Chinese breast cancer patients in Singapore. BRCA1 analysis was conducted in consecutive patients with breast cancer before the age of 40 years (76 women), or whose relatives had breast or ovarian cancer (16 women). Ten patients had both early onset breast cancer and affected relatives. Genomic DNA from peripheral mononuclear blood cells was studied by using the protein transcription–translation assay (exon 11) and single-strand conformational polymorphism, with subsequent DNA sequencing. All six disease-causing mutations occurred in women under 40 years (8.6%) with three occurring in patients under 35 years (three out of 22 patients, 13.6%). Mis-sense mutations of unknown significance were found in three patients. Two of the ten women with affected relatives under 40 years had BRCA1 mutations. The prevalence of BRCA1 mutations in Chinese patients with early onset breast cancer is similar to that observed in Caucasian women. Most Chinese patients with affected relatives were not carriers of BRCA1 mutations. © 2000 Cancer Research Campaig

Use of Complex Lie Symmetries for Linearization of Systems of Differential Equations - II: Partial Differential Equations

The linearization of complex ordinary differential equations is studied by extending Lie's criteria for linearizability to complex functions of complex variables. It is shown that the linearization of complex ordinary differential equations implies the linearizability of systems of partial differential equations corresponding to those complex ordinary differential equations. The invertible complex transformations can be used to obtain invertible real transformations that map a system of nonlinear partial differential equations into a system of linear partial differential equation. Explicit invariant criteria are given that provide procedures for writing down the solutions of the linearized equations. A few non-trivial examples are mentioned.Comment: This paper along with its first part ODE-I were combined in a single research paper "Linearizability criteria for systems of two second-order differential equations by complex methods" which has been published in Nonlinear Dynamics. Due to citations of both parts I and II these are not replaced with the above published articl

Microglial amyloid beta clearance is driven by PIEZO1 channels

Background Microglia are the endogenous immune cells of the brain and act as sensors of pathology to maintain brain homeostasis and eliminate potential threats. In Alzheimer's disease (AD), toxic amyloid beta (A beta) accumulates in the brain and forms stiff plaques. In late-onset AD accounting for 95% of all cases, this is thought to be due to reduced clearance of A beta. Human genome-wide association studies and animal models suggest that reduced clearance results from aberrant function of microglia. While the impact of neurochemical pathways on microglia had been broadly studied, mechanical receptors regulating microglial functions remain largely unexplored. Methods Here we showed that a mechanotransduction ion channel, PIEZO1, is expressed and functional in human and mouse microglia. We used a small molecule agonist, Yoda1, to study how activation of PIEZO1 affects AD-related functions in human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGL) under controlled laboratory experiments. Cell survival, metabolism, phagocytosis and lysosomal activity were assessed using real-time functional assays. To evaluate the effect of activation of PIEZO1 in vivo, 5-month-old 5xFAD male mice were infused daily with Yoda1 for two weeks through intracranial cannulas. Microglial Iba1 expression and A beta pathology were quantified with immunohistochemistry and confocal microscopy. Published human and mouse AD datasets were used for in-depth analysis of PIEZO1 gene expression and related pathways in microglial subpopulations. Results We show that PIEZO1 orchestrates A beta clearance by enhancing microglial survival, phagocytosis, and lysosomal activity. A beta inhibited PIEZO1-mediated calcium transients, whereas activation of PIEZO1 with a selective agonist, Yoda1, improved microglial phagocytosis resulting in A beta clearance both in human and mouse models of AD. Moreover, PIEZO1 expression was associated with a unique microglial transcriptional phenotype in AD as indicated by assessment of cellular metabolism, and human and mouse single-cell datasets. Conclusion These results indicate that the compromised function of microglia in AD could be improved by controlled activation of PIEZO1 channels resulting in alleviated A beta burden. Pharmacological regulation of these mechanoreceptors in microglia could represent a novel therapeutic paradigm for AD.Peer reviewe

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain–behavior relationships after stroke

The goal of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well‐powered meta‐ and mega‐analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large‐scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided

Evaluation of health workforce competence in maternal and neonatal issues in public health sector of Pakistan: an Assessment of their training needs

<p>Abstract</p> <p>Background</p> <p>More than 450 newborns die every hour worldwide, before they reach the age of four weeks (neonatal period) and over 500,000 women die from complications related to childbirth. The major direct causes of neonatal death are infections (36%), Prematurity (28%) and Asphyxia (23%). Pakistan has one of the highest perinatal and neonatal mortality rates in the region and contributes significantly to global neonatal mortality. The high mortality rates are partially attributable to scarcity of trained skilled birth attendants and paucity of resources. Empowerment of health care providers with adequate knowledge and skills can serve as instrument of change.</p> <p>Methods</p> <p>We carried out training needs assessment analysis in the public health sector of Pakistan to recognize gaps in the processes and quality of MNCH care provided. An assessment of Knowledge, Attitude, and Practices of Health Care Providers on key aspects was evaluated through a standardized pragmatic approach. Meticulously designed tools were tested on three tiers of health care personnel providing MNCH in the community and across the public health care system. The Lady Health Workers (LHWs) form the first tier of trained cadre that provides MNCH at primary care level (BHU) and in the community. The Lady Health Visitor (LHVs), Nurses, midwives) cadre follow next and provide facility based MNCH care at secondary and tertiary level (RHCs, Taluka/Tehsil, and DHQ Hospitals). The physician/doctor is the specialized cadre that forms the third tier of health care providers positioned in secondary and tertiary care hospitals (Taluka/Tehsil and DHQ Hospitals). The evaluation tools were designed to provide quantitative estimates across various domains of knowledge and skills. A priori thresholds were established for performance rating.</p> <p>Results</p> <p>The performance of LHWs in knowledge of MNCH was good with 30% scoring more than 70%. The Medical officers (MOs), in comparison, performed poorly in their knowledge of MNCH with only 6% scoring more than 70%. All three cadres of health care providers performed poorly in the resuscitation skill and only 50% were able to demonstrate steps of immediate newborn care. The MOs performed far better in counselling skills compare to the LHWs. Only 50 per cent of LHWs could secure competency scale in this critical component of skills assessment.</p> <p>Conclusions</p> <p>All three cadres of health care providers performed well below competency levels for MNCH knowledge and skills. Standardized training and counselling modules, tailored to the needs and resources at district level need to be developed and implemented. This evaluation highlighted the need for periodic assessment of health worker training and skills to address gaps and develop targeted continuing education modules. To achieve MDG4 and 5 goals, it is imperative that such deficiencies are identified and addressed.</p

Convergent Evidence from Mouse and Human Studies Suggests the Involvement of Zinc Finger Protein 326 Gene in Antidepressant Treatment Response

OBJECTIVES: The forced swim test (FST) is a commonly used model to predict antidepressant efficacy. Uncovering the genetic basis of the model may unravel the mechanism of antidepressant treatment. METHODS: FVB/NJ (FVB) and C57BL/6J (B6) were first identified as the response and non-response strains to fluoxetine (a serotonin-specific reuptake inhibitor antidepressant) treatment in the mouse FST. Simple-interval (SIM) and composite-interval (CIM) mappings were applied to map the quantitative trait loci (QTLs) of the anti-immobility effect of fluoxetine in FST (FST(FLX)) in 865 male B6×FVB-F2 mice. The brain mRNA expressions of the gene with the maximum QTL-linkage signal for FST(FLX) after the FST were compared between B6 and FVB mice and also compared between fluoxetine and saline treatment. The association of the variants in the human homologue of the mouse FST(FLX)-QTL gene with major depressive disorder (MDD) and antidepressant response were investigated in 1080 human subjects (MDD/control = 582/498). RESULTS: One linkage signal for FST(FLX)-QTL was detected at an intronic SNP (rs6215396) of the mouse Zfp326 gene (maximal CIM-LOD = 9.36). The Zfp326 mRNA expression in the FVB thalamus was significantly down-regulated by fluoxetine in the FST, and the higher FVB-to-B6 Zfp326 mRNA expressions in the frontal cortex, striatum and hypothalamus diminished after fluoxetine treatment. Two coding-synonymous SNPs (rs2816881 and rs10922744) in the human homologue of Zfp326, ZNF326, were significantly associated with the 8-week antidepressant treatment response in the MDD patients (Bonferroni-corrected p = 0.004-0.028). CONCLUSIONS: The findings suggest the involvement of the Zfp326 and ZNF326 genes in antidepressant treatment response